ABSTRACT
Intracellular current- and voltage-clamp recordings were obtained from basolateral (BLA) and central (ACe) neurones of the rat amygdala in vitro. The effect of superfusion of rat corticotropin releasing factor (rCRF) was examined on the ACe and BLA, nuclei with a high density of CRF-immunoreactive cell bodies and CRF receptors, respectively. rCRF (12.5-250 nM) had no effect on either resting membrane potential or input resistance in BLA neurones. In contrast, at low nanomolar concentrations rCRF (10-50 nM) caused hyperpolarisation and decreased membrane input resistance in the majority of ACe neurones. The equilibrium potential for this effect was -84 mV in the presence of tetrodotoxin (0.5 microM), suggesting that this response may be mediated by a postsynaptic increase in K+ conductance. Furthermore, rCRF consistently reduced the amplitude of, and the current mediating, the slow after hyperpolarisation following evoked action potential firing in both nuclei. This effect was concentration-dependent with an EC50 of 40 nM in BLA neurones and was insensitive to tetrodotoxin and noradrenergic antagonists. In addition, the putative CRF antagonist alpha-helical CRF9-41 (5 microM) blocked the effect of rCRF and showed partial agonist action on slow after hyperpolarisations. In BLA neurones, rCRF (50 nM) prolonged the Ca(2+)-spike evoked in the presence of tetrodotoxin and tetraethylammonium (2 mM), suggesting that the blockade of the slow after hyperpolarisation occurs subsequent to Ca2+ entry. These results suggest that rCRF has a differential effect on the membrane properties of BLA and ACe neurones possibly by activation of a heterogeneous population of CRF receptors.
Subject(s)
Amygdala/drug effects , Corticotropin-Releasing Hormone/pharmacology , Animals , Cell Membrane/drug effects , Corticotropin-Releasing Hormone/antagonists & inhibitors , Evoked Potentials/drug effects , Male , Membrane Potentials/drug effects , Neurons/drug effects , Peptide Fragments/pharmacology , Phentolamine/pharmacology , Propranolol/pharmacology , Rats , Rats, Sprague-Dawley , Receptors, Corticotropin-Releasing Hormone , Receptors, Neurotransmitter/antagonists & inhibitors , Receptors, Neurotransmitter/drug effectsABSTRACT
Lysophosphatidic acid (LPA) is a naturally occurring phospholipid that can elicit platelet aggregation, smooth muscle contraction and, in fibroblasts, cell proliferation. We now report that LPA in nanomolar concentrations evokes an inward current in native, defolliculated Xenopus laevis oocytes. Extracellular application of LPA from a pressure pipette to the surface of the oocyte induced an immediate response. In contrast, intracellular injection of the same amount of LPA failed to elicit a response. These data suggest the existence of a Ca(2+)-mobilizing, endogenous LPA receptor in the Xenopus laevis oocyte cell membrane.
